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The DiRECT Study: Analysis of Patients With Type 2 Diabetes Remission — ADA 2019

Jun 18, 2019
 
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Adam Chalela, B.S. Doctor of Pharmacy Candidate USF College of Pharmacy

DiRECT study data announced at the 79th annual Scientific Sessions of the ADA shows restoration of beta cell function is possible.

The progression of type 2 diabetes can be attributed to a decline in pancreatic beta cell function. Impaired glucose tolerance as seen in patients with prediabetes results from a loss of sensitivity to glucose and lack of insulin production by these beta cells. Constant hyperglycemic states add further insult to beta cell injury which can lead to permanent loss of function. In early stages of the disease, however, it may be possible to restore healthy beta cell function as damage has yet to be permanent.

A recent study, presented at the 79th annual ADA Scientific Sessions conference for the first time, completed a secondary analysis of a specific patient subgroup from the Diabetes Remission Clinical Trial (DiRECT) that was originally published in early 2018. The DiRECT study aimed to determine treatment differences between patients with type 2 diabetes that were treated with either weight management therapy or guideline-directed therapy through primary care (control). Patients were enrolled into this study if they were aged between 20 and 65 years old, had a BMI of between 27 and 45 kg/m2, had type 2 diabetes for a maximum of 6 years, and were not receiving any forms of insulin therapy.

The researchers of the DiRECT study observed weight loss of >15kg within 24% of patients that underwent weight management therapy and within 0% of patients randomized to receive guideline-directed pharmacotherapy at 12 months. Complete remission of diabetes, as defined by an HbA1c of <6.5% after withdrawal of all antidiabetic medications for at least 2 months and fasting plasma glucose values of <126 mg/dL, was observed in 46% of participants in the weight management group and only 4% of patients in the control group (OR 19.7, 95% CI 7.8 – 49.8). These findings demonstrate that remission of type 2 diabetes back to a normal glycemic state can be easily achieved without pharmacotherapy initiation in newly diagnosed patients.

Patients that achieved clinical remission of type 2 diabetes during the DiRECT trial were analyzed more recently to determine their level of beta cell function. Beta cell function was quantified by maximal insulin secretory response during hyperglycemia through arginine induced insulin secretion. About half of patients who initially gained remission of type 2 diabetes remained in remission throughout two years of follow up; the other half either regained their weight back and relapsed or were lost during follow up. After stratification for age and gender, secondary analysis determined that insulin secretion rates were comparable between patients who gained remission of type 2 diabetes and a control group of patients who had never suffered from diabetes at 24 months follow up (0.94 nmoL/min/m2 and 1.02 nmoL/min/m2, respectively).

Beta cells are directly responsible for providing sufficient amounts of insulin to maintain adequate glucose homeostasis. The results of this study demonstrate that both intensive weight management strategies and guideline directed therapy are able to achieve remission of type 2 diabetes. Results also further prove that type 2 diabetes is a reversible disease and patients who once suffered may be able to regain their previous quality of life. Remission of type 2 diabetes has also been proven to significantly reduce the risk of secondary complications later down the line.

Practice Pearls

  • Patients who underwent remission of type 2 diabetes had significantly similar insulin secretory responses to patients without diabetes.
  • Limited study population of the original DiRECT trial led to poor generalizability of both trial results.
  • Patients with early stages of type 2 diabetes should be encouraged to initiate weight management therapy and to minimize weight regain for diabetes remission and best improvements in quality of life.
  1. Zhyzhneuskaya SV, Al-Mrabeh A, Barnes AC, et al. Remission of type 2 diabetes for two years is associated with full recovery of beta-cell functional mass in the Diabetes Remission Clinical Trial (DiRECT). Diabetes 2019; [Epub ahead of print]. DOI: 10.2337/db19-66-OR
  2. Lean MEJ, Leslie WS, Barnes AC, et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomized trial. The Lancet 2018; 391(10120):541-551. DOI: 10.1016/S0140-6736(17)33102-1

 

Reported at the American Diabetes Association 79th Scientific Sessions June, 2019

 

Adam Chalela B.S., PharmD Candidate, USF College of Pharmacy Class of 2020